tbuckley/cabot-search huggingface dataset:
Assessment and Prognostic Value of Inflammatory Biomarkers in Patients With Colon Cancer—Reply
Authors: En Cheng, Jeffrey A. Meyerhardt
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Comprehensive functional characterization of SGCB coding variants predicts pathogenicity in limb-girdle muscular dystrophy type R4/2E
Authors: Chengcheng Li, Jackson Wilborn, Sara Pittman, Jil Daw, Jorge Alonso-Pérez, Jordi Díaz-Manera, Conrad C. Weihl, Gabe Haller
Journal: Journal of Clinical Investigation (2023)

Genetic testing is essential for patients with a suspected hereditary myopathy. More than 50% of patients clinically diagnosed with a myopathy carry a variant of unknown significance in a myopathy gene, often leaving them without a genetic diagnosis. Limb-girdle muscular dystrophy (LGMD) type R4/2E is caused by mutations in β-sarcoglycan (SGCB). Together, β-, α-, γ-, and δ-sarcoglycan form a 4-protein transmembrane complex (SGC) that localizes to the sarcolemma. Biallelic loss-of-function mutations in any subunit can lead to LGMD. To provide functional evidence for the pathogenicity of missense variants, we performed deep mutational scanning of SGCB and assessed SGC cell surface localization for all 6,340 possible amino acid changes. Variant functional scores were bimodally distributed and perfectly predicted pathogenicity of known variants. Variants with less severe functional scores more often appeared in patients with slower disease progression, implying a relationship between variant function and disease severity. Amino acid positions intolerant to variation mapped to points of predicted SGC interactions, validated in silico structural models, and enabled accurate prediction of pathogenic variants in other SGC genes. These results will be useful for clinical interpretation of SGCB variants and improving diagnosis of LGMD; we hope they enable wider use of potentially life-saving gene therapy.
Focusing on Decisions, Outcomes, and Value Judgments to Confront Algorithmic Bias
Authors: Ankur Pandya, Jinyi Zhu
Journal: JAMA Network Open (2023)

Sara Khor, MASc; Eric C. Haupt, ScM; Erin E. Hahn, PhD, MPH; Lindsay Joe L. Lyons, LVN; Veena Shankaran, MD, MS; Aasthaa Bansal, PhD
Assessment and Prognostic Value of Inflammatory Biomarkers in Patients With Colon Cancer
Authors: Josh McGovern, Ross D. Dolan, Donald C. McMillan
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Live Biotherapeutic Products as Cancer Treatments
Authors: Arianna Brevi, Amir Zarrinpar
Journal: Cancer Research (2023)

Almost every aspect of cancer can be influenced by microbiota including tumor onset, progression, and response to therapy. The increasing evidence of the role of microbiota in human health and disease has reinvigorated the interest in designing microbial products that can affect cancer outcomes. Researchers have made numerous attempts to develop safe, engineered biotherapeutic products for cancer treatment using synthetic biology tools. Despite the progress, only Bacillus Calmette-Guérin is approved for human use. Here, we highlight the recent advances and current challenges in using live bacteria as cancer therapeutics.
Dapagliflozin and Physical and Social Activity Limitations in Heart Failure With Reduced Ejection Fraction
Authors: Jawad H. Butt, Kieran F. Docherty, Mikhail N. Kosiborod, Silvio E. Inzucchi, Lars Køber, Anna Maria Langkilde, Felipe A. Martinez, Olof Bengtsson, Piotr Ponikowski, Marc S. Sabatine, Mikaela Sjöstrand, Scott Solomon, Pardeep S. Jhund, John J.V. McMurray
Journal: JACC Heart Failure (2023)

Heart failure (HF) is associated with impaired physical function and poor quality of life and affects health status more profoundly than many other chronic diseases.The authors examined the effects of dapagliflozin on specific physical and social limitations as reported by patients in the DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure) trial.The effect of dapagliflozin on the change from baseline to 8 months in each of the individual physical and social activity limitation questions answered by patients completing the Kansas City Cardiomyopathy Questionnaire (KCCQ), and overall scores, were examined with mixed-effects models and responder analyses.In total, 4,269 (90.0%) and 3,955 (83.4%) patients had complete data for both the physical and social activity limitation scores at baseline and 8 months, respectively. Compared with placebo, dapagliflozin significantly increased (improved) the mean KCCQ physical and social activity limitation scores at 8 months (placebo-corrected mean difference 1.94 [95% CI: 0.73-3.16] and 1.84 [95% CI: 0.43-3.25], respectively). Dapagliflozin also increased each of the individual components that comprise the physical and social activity limitations domains at 8 months, with the largest improvement seen in "hobbies or recreational activities" (placebo-corrected mean difference: 2.76 [95% CI: 1.06-4.46]) and "doing yardwork, housework, or carrying groceries" (placebo-corrected mean difference: 2.59 [95% CI: 0.76-4.42]). The proportion of patients with a 5-point improvement from baseline to 8 months in the KCCQ physical and social activity limitation scores was greater with dapagliflozin than with placebo (ORs: 1.23 [95% CI: 1.09-1.40] and 1.19 [95% CI: 1.05-1.35], respectively).In patients with HFrEF, dapagliflozin, compared with placebo, improved physical and social activity limitations as measured by KCCQ. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients with Chronic Heart Failure [DAPA-HF]; NCT03036124).
Leveraging CD16 fusion receptors to remodel the immune response for enhancing anti-tumor immunotherapy in iPSC-derived NK cells
Authors: Fanyi Meng, Siqi Zhang, Juan Xie, Yuan Zhou, Qingling Wu, Binyan Lu, Shixin Zhou, Xiangyu Zhao, Yang Li
Journal: Journal of Hematology & Oncology (2023)

Abstract Background The cytotoxicity of NK cells is largely dependent on IgG Fc receptor CD16a, which mediates antibody-dependent cell-mediated cytotoxicity (ADCC). The high-affinity and non-cleavable CD16 (hnCD16) is developed and demonstrated a multi-tumor killing potential. However, the hnCD16 receptor activates a single CD16 signal and provides limited tumor suppression. How to exploit the properties of hnCD16 and incorporate NK cell-specific activation domains is a promising development direction to further improve the anti-tumor activity of NK cells. Methods To expand the applications of hnCD16-mediated ADCC for NK cell-based immunotherapy in cancer, we designed the hnCD16 Fusion Receptor (FR) constructs with the ectodomain of hnCD16 fused with NK cell-specific activating domains in the cytoplasm. FR constructs were transduced into CD16-negative NK cell line and human iPSC-derived NK (iNK) cells and effective FR constructs were screened. The up-regulation of immune activation- and cytokine-releasing-related pathways in FR-transduced NK cells was screened and validated by RNA sequencing and multiplex cytokines release assay, respectively. The tumor-killing efficiency was tested in vitro and in vivo via co-culture with tumor cell lines and xenograft mice-bearing human B-cell lymphoma, respectively. Results We screened the most effective combination to kill B cell lymphoma, which was fused with the ectodomain of hnCD16a, NK-specific co-stimulators (2B4 and DAP10) and CD3ζ in cytoplasmic domains. The screened construct showed excellent cytotoxicity effects and sharp multiple cytokines releasing both in the NK cell line and iNK cells. The transcriptomic analysis and validation assays of hnCD16- and hnCD16FR-transduced NK cells showed that hnCD16FR transduction remodeled immune-related transcriptome in NK cells, where significant upregulation of genes related to cytotoxicity, high cytokines releasing, induced tumor cell apoptosis, and ADCC in comparison with hnCD16 transduction were highlighted. In vivo xenograft studies demonstrated that a single low-dose regimen of engineered hnCD16FR iPSC-derived NK cells co-administered with anti-CD20 mAb treatment mediated potent activity and significantly improved survival. Conclusion We developed a novel hnCD16FR construct that exhibits more potent cytotoxicity than reported hnCD16, which is a promising approach to treat malignancies with improved ADCC properties. We also offer a rationale for NK activation domains that remodel immune response to enhance CD16 signaling in NK cells.
Brain microglia serve as a persistent HIV reservoir despite durable antiretroviral therapy
Authors: Yuyang Tang, Antoine Chaillon, Sara Gianella, Lilly M. Wong, Dajiang Li, Theresa L. Simermeyer, Magali Porrachia, Caroline Ignacio, Brendon Woodworth, Daniel Zhong, Jiayi Du, Eduardo de la Parra Polina, Jennifer Kirchherr, Brigitte Allard, Matthew L. Clohosey, Matt Moeser, Amy L. Sondgeroth, Gregory D. Whitehill, Vidisha Singh, Amir Dashti, Davey M. Smith, Joseph J. Eron, Katherine J. Bar, Ann Chahroudi, Sarah B. Joseph, Nancie M. Archin, David M. Margolis, Guochun Jiang
Journal: Journal of Clinical Investigation (2023)

Brain microglia (MG) may serve as a human immunodeficiency virus 1 (HIV) reservoir and ignite rebound viremia following cessation of antiretroviral therapy (ART), but they have yet to be proven to harbor replication-competent HIV. Here, we isolated brain myeloid cells (BrMCs) from nonhuman primates and rapid autopsy of people with HIV (PWH) on ART and sought evidence of persistent viral infection. BrMCs predominantly displayed microglial markers, in which up to 99.9% of the BrMCs were TMEM119+ MG. Total and integrated SIV or HIV DNA was detectable in the MG, with low levels of cell-associated viral RNA. Provirus in MG was highly sensitive to epigenetic inhibition. Outgrowth virus from parietal cortex MG in an individual with HIV productively infected both MG and PBMCs. This inducible, replication-competent virus and virus from basal ganglia proviral DNA were closely related but highly divergent from variants in peripheral compartments. Phenotyping studies characterized brain-derived virus as macrophage tropic based on the ability of the virus to infect cells expressing low levels of CD4. The lack of genetic diversity in virus from the brain suggests that this macrophage-tropic lineage quickly colonized brain regions. These data demonstrate that MG harbor replication-competent HIV and serve as a persistent reservoir in the brain.
Symptoms, Outcomes, and Regurgitant Severity in Guideline-Directed Mitral Valve Surgery
Authors: Seth Uretsky, Robert W.W. Biederman, Yuchi Han, Ron Jacob, Edward T. Martin, Michael Langer, Andrew D. Choi, Ibrahim Sultan, Joao L. Cavalcante, Dipan J. Shah, Matthew S. Tong, Steven D. Wolff, Marco Guglielmo, Gianluca Pontone
Journal: JACC. Cardiovascular imaging (2023)
Opportunities and Achievement of Medication Initiation Among Inpatients With Heart Failure With Reduced Ejection Fraction
Authors: Stanley A. Swat, Haolin Xu, Larry A. Allen, Stephen J. Greene, Adam D. DeVore, Roland A. Matsouaka, Parag Goyal, Pamela N. Peterson, Adrian F. Hernandez, Harlan M. Krumholz, Clyde W. Yancy, Gregg C. Fonarow, Paul L. Hess
Journal: JACC Heart Failure (2023)
Association between the timing of childhood adversity and epigenetic patterns across childhood and adolescence: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort
Authors: Alexandre A Lussier, Yiwen Zhu, Brooke J Smith, Janine Cerutti, Jonah Fisher, Phillip E Melton, Natasha M Wood, Sarah Cohen-Woods, Rae-Chi Huang, Colter Mitchell, Lisa Schneper, Daniel A Notterman, Andrew J Simpkin, Andrew D A C Smith, Matthew J Suderman, Esther Walton, Caroline L Relton, Kerry J Ressler, Erin C Dunn
Journal: The Lancet Child & Adolescent Health (2023)
An international research agenda for clozapine-resistant schizophrenia
Authors: Jurjen J Luykx, Jairo M Gonzalez-Diaz, Ta-Wei Guu, Marte Z van der Horst, Edwin van Dellen, Marco P Boks, Sinan Guloksuz, Lynn E DeLisi, Iris E Sommer, Russel Cummins, David Shiers, Jimmy Lee, Susanna Every-Palmer, Ahmed Mhalla, Zohra Chadly, Sherry K W Chan, Robert O Cotes, Shun Takahashi, Michael E Benros, Elias Wagner, Christoph U Correll, Alkomiet Hasan, Dan Siskind, Dominique Endres, James MacCabe, Jari Tiihonen
Journal: The Lancet Psychiatry (2023)
Arf6 as a therapeutic target: Structure, mechanism, and inhibitors
Authors: Dejuan Sun, Yuanyuan Guo, Piyu Tang, Hua Li, Lixia Chen
Journal: Acta Pharmaceutica Sinica B (2023)

ADP-ribosylation factor 6 (Arf6), a small G-protein of the Ras superfamily, plays pivotal roles in multiple cellular events, including exocytosis, endocytosis, actin remodeling, plasma membrane reorganization and vesicular transport. Arf6 regulates the progression of cancer through the activation of cell motility and invasion. Aberrant Arf6 activation is a potential therapeutic target. This review aims to understand the comprehensive function of Arf6 for future cancer therapy. The Arf6 GEFs, protein structure, and roles in cancer have been summarized. Comprehending the mechanism underlying Arf6-mediated cancer cell growth and survival is essential. The structural features of Arf6 and its efforts are discussed and may be contributed to the discovery of future novel protein-protein interaction inhibitors. In addition, Arf6 inhibitors and mechanism of action are listed in the table. This review further emphasizes the crucial roles in drug resistance and attempts to offer an outlook of Arf6 in cancer therapy.
Endoscopic debulking of a large colonic lipoma causing recurrent intussusception using endoscopic mucosotomy technique
Authors: Jenson Phung, Morgan Freeman, Mohammad Bilal
Journal: Endoscopy (2023)

Colonic lipomas are usually incidental findings during colonoscopy. Lipomas ≥ 4 cm can cause obstruction and intussusception. Surgical resection is often recommended in these instances [1] [2]. However, endoscopic resection of larger lipomas has been reported previously using PolyLoop-assisted unroofing technique, snare catheter unroofing/resection, and placement of endoclips prior to resection [3]. Here, we describe a novel technique for endoscopic debulking of a large colonic lipoma.
Trastuzumab deruxtecan in patients in the USA and Europe with HER2-positive advanced gastric or gastroesophageal junction cancer with disease progression on or after a trastuzumab-containing regimen (DESTINY-Gastric02): primary and updated analyses from a single-arm, phase 2 study
Authors: Eric Van Cutsem, Maria di Bartolomeo, Elizabeth Smyth, Ian Chau, Haeseong Park, Salvatore Siena, Sara Lonardi, Zev A Wainberg, Jaffer Ajani, Joseph Chao, Yelena Janjigian, Amy Qin, Jasmeet Singh, Ferdous Barlaskar, Yoshinori Kawaguchi, Geoffrey Ku
Journal: The Lancet Oncology (2023)
Endoscopic ultrasound-guided biliary recanalization with a novel rendezvous inflated balloon-assisted technique for isolated bile leakage
Authors: Naruomi Jinno, Michihiro Yoshida, Kazuki Hayashi, Itaru Naitoh, Yasuki Hori, Makoto Natsume, Hiromi Kataoka
Journal: Endoscopy (2023)

Bile leakage after hepatectomy has been reported to occur in 5 %–8 % of cases [1] [2]. In particular, isolated bile leakage is intractable and may require surgical re-anastomosis. In general, endoscopic treatment for isolated bile leakage by transpapillary biliary drainage for recanalization is challenging [3]; the procedure is often unsuccessful because of surgically altered anatomy and disconnection of the bile duct. Here, we report a case of successful endoscopic ultrasound (EUS)-guided biliary recanalization for isolated bile leakage that employed a novel approach assisted by rendezvous balloon inflation.
Enhancing the Efficacy of Mesenchymal Stromal Cells in COVID-19–related Acute Respiratory Distress Syndrome
Authors: Haibo Zhang, Arthur S. Slutsky
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Enhancing the Efficacy of Mesenchymal Stromal Cells in COVID-19-related Acute Respiratory Distress Syndrome." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Association between lipocalin-2 and mild cognitive impairment or dementia: A systematic review and meta-analysis of population-based evidence
Authors: Xiuwen Li, Xiaojie Wang, Lan Guo, Keying Wu, Li Wang, Lu Rao, Xinjian Liu, Chenyao Kang, Bin Jiang, Qian Li, Huling Li, Fenfen He, Ciyong Lu
Journal: Ageing Research Reviews (2023)
Reply to Chen <i>et al.</i>
Authors: Geoffroy Solelhac, Manuel Sánchez-de-la-Torre, Margaux Blanchard, Ferran Barbé, Frédéric Gagnadoux, Raphael Heinzer
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Reply to: OSA with High Pulse Wave Amplitude Drops Index: A Specific Phenotype for Cardiovascular Benefit from CPAP?." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Endoscopic resection for an esophageal inclusion cyst
Authors: Lifan Zhang, Huanhuan Yang, Liansong Ye, Ou Chen, Bing Hu
Journal: Endoscopy (2023)

A 24-year-old woman complained of intermittent dysphagia for 2 years. She reported a previous medical history of asthma, hyperthyroidism, and myocarditis. Physical examination revealed no special abnormalities. Computed tomography detected a 5.2 × 4.2-cm mass with a clear boundary in the esophagus ([Fig. 1 a]). Endoscopy showed a large lesion 30–34 cm from the incisors ([Fig. 1 b]). Endoscopic ultrasonography confirmed the hypoechoic lesion with hyperechoic foci, originating from the submucosal layer ([Fig. 1 c]). Endoscopic resection was performed for this patient ([Fig. 2], [Video 1]). After submucosal injection at 3 cm proximal to the lesion, a mucosal incision was made using a dual knife. A submucosal tunnel was subsequently created. When the lesion was partially exposed with an insulated-tip knife, it ruptured suddenly and yellow milky fluid flowed out, suggesting an esophageal cyst. The top layer of the cyst was resected using the dual knife. Then, the remaining rest cyst wall was destroyed using electrocoagulation forceps and anhydrous alcohol. The mucosa beyond the cyst was also removed using a snare. There was no bleeding or perforation during the procedure. Histopathology showed a pseudostratified ciliated columnar epithelium-lined cyst wall and no cartilage or bilayer smooth muscle, confirming it was esophageal inclusion cyst. The patient recovered uneventfully. During 2 months of follow-up, the patient reported no further discomfort; endoscopy also showed complete healing of the wound ([Fig. 3]).
Antidiabetic agents as a novel treatment for Alzheimer’s and Parkinson’s disease
Authors: Joseph Nowell, Eleanor Blunt, Dhruv Gupta, Paul Edison
Journal: Ageing Research Reviews (2023)

Therapeutic strategies for neurodegenerative disorders have commonly targeted individual aspects of the disease pathogenesis to little success. Neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), are characterized by several pathological features. In AD and PD, there is an abnormal accumulation of toxic proteins, increased inflammation, decreased synaptic function, neuronal loss, increased astrocyte activation, and perhaps a state of insulin resistance. Epidemiological evidence has revealed a link between AD/PD and type 2 diabetes mellitus, with these disorders sharing some pathological commonalities. Such a link has opened up a promising avenue for repurposing antidiabetic agents in the treatment of neurodegenerative disorders. A successful therapeutic strategy for AD/PD would likely require a single or several agents which target the separate pathological processes in the disease. Targeting cerebral insulin signalling produces numerous neuroprotective effects in preclinical AD/PD brain models. Clinical trials have shown the promise of approved diabetic compounds in improving motor symptoms of PD and preventing neurodegenerative decline, with numerous further phase II trials and phase III trials underway in AD and PD populations. Alongside insulin signalling, targeting incretin receptors in the brain represents one of the most promising strategies for repurposing currently available agents for the treatment of AD/PD. Most notably, glucagon-like-peptide-1 (GLP-1) receptor agonists have displayed impressive clinical potential in preclinical and early clinical studies. In AD the GLP-1 receptor agonist, liraglutide, has been demonstrated to improve cerebral glucose metabolism and functional connectivity in small-scale pilot trials. Whilst in PD, the GLP-1 receptor agonist exenatide is effective in restoring motor function and cognition. Targeting brain incretin receptors reduces inflammation, inhibits apoptosis, prevents toxic protein aggregation, enhances long-term potentiation and autophagy as well as restores dysfunctional insulin signalling. Support is also increasing for the use of additional approved diabetic treatments, including intranasal insulin, metformin hydrochloride, peroxisome proliferator-activated nuclear receptor γ agonists, amylin analogs, and protein tyrosine phosphatase 1B inhibitors which are in the investigation for deployment in PD and AD treatment. As such, we provide a comprehensive review of several promising anti-diabetic agents for the treatment of AD and PD.
Obstructive Sleep Apnea with High Pulse Wave Amplitude Drops Index: A Specific Phenotype for Cardiovascular Benefit from Continuous Positive Airway Pressure?
Authors: Yating Chen, Jingcun Wang, Shenyu Wen, Donghao Wang, Qiming Gan, Yiqi Lin, Jianxiong Lai, Haojie Zhang, Yanyan Zhou, Dongxing Zhao
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"OSA with High Pulse Wave Amplitude Drops Index: A Specific Phenotype for Cardiovascular Benefit from CPAP?." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.